Coated sustained release tablets of a hygroscopic compound for once-a-day therapy

Abstract

The present invention provides coated sustained release tablets of a hygroscopic compound for once-a-day therapy, said tablets having a moderate weight and volume and comprising-(a) a core comprising the hygroscopic compound and pharmaceutically acceptable excipients, (b) a first coating layer comprising a polymer selected from the group consisting of water-insoluble polymers, pH dependent polymers or a mixture thereof, and (c) a second coating layer comprising a water-insoluble polymer.

Description

[0001] The present invention relates to coated sustained release tablets of a hygroscopic compound for once-a-day therapy. Particularly, it relates to coated sustained release tablets of sodium valproate for once-a-day therapy.[0002] Valproic acid and its derivatives, such as sodium valproate, calcium valproate, divlaproex sodium, valpromide, are used widely in the treatment of epilepsy. The effective concentration of the drug in the blood is generally in the range of 50 to 100 .mu.g / ml. Various derivatives of valproic acid such as sodium valproate, calcium valproate, divalproex sodium, valpromide, and combinations thereof are used in the treatment of epilepsy. All these derivatives of valproic acid eventually get converted to valproic acid or the valproate ion, in the gastrointestinal tract.[0003] Sodium valproate is a commonly used derivative of valproic acid, which has a short half-life, and has to be administered three times a day to maintain effective plasma levels of the drug....

AI Technical Summary

Benefits of technology

[0011] It is a further object of the invention to provide coated sustained release tablets of sodium valproate for once-a-day therapy, such that the tablets have a moderate weight and volume.

[0017] The present invention provides coated sustained release tablets of sodium valproate that are moisture-stable, have a moderate weight and volume and are therefore, easy to swallow. The dual coatings used in the present invention provide moisture stability to the tablets and at the same time provide a sustained release of sodium valproate, such that the tablet is suitable for once-a-day therapy.

[0023] Preferably the hygroscopic compound of the present invention is sodium valproate. The core comprising sodium valproate and pharmaceutically acceptable excipients is surrounded by a dual coating, wherein the first coating layer comprises a polymer selected from the group consisting of water-insoluble polymers, pH dependent polymers or a mixture thereof, and the second coating layer comprises a water-insoluble polymer. The second coating may further comprise a polymer selected from the group consisting of a water-soluble polymer, a pH dependent polymer, or mixtures thereof. Such a dual coating provides moisture-stable sodium valproate tablets, and at the same time avoids the use of moisture absorbing excipients in the core, thus limiting the weight and size of the tablets. The dual coating also provides sustained release of sodium valproate from the core for a period of more than 8 hours, the tablets therefore providing once-a-day therapy of sodium valproate.

Problems solved by technology

However, sodium valproate is water-soluble and highly hygroscopic, and cannot be formulated using conventional sustained release techniques.

Also, the treatment of epilepsy requires a large daily dose of sodium valproate reaching 1200 mg, thereby further complicating the formulation procedures.

Hence, conventional sustained release tablets of sodium valproate require the use of a large amount of release retarders and excipients, thereby increasing the weight of the tablet.

However, the dosage form is not coated and would be susceptible to the adverse effects of moisture, as a result of the hygroscopic nature of sodium valproate.

Also, the sustained release dosage form obtained by the process of the patent is relatively large and difficult to swallow.

The use of organic solvents is hazardous from safety and environmental aspects.

Such large tablets are difficult to swallow.

The system does not provide two coating layers that provide moisture-stable sodium valproate sustained release tablets.